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Biomedical subjects

D T Lowenthal

Publications and source records attributed to D T Lowenthal.

At least 91 records · Page 5Linked to original sources
PubMed1987

Cardiovascular drugs and exercise interactions.

An appreciation of the hemodynamic and biochemical changes induced by drugs is critical for a logical diagnostic interpretation of graded stress tests and the evaluation of the projected exercise prescription and exercise programs that a patient is asked to follow. Drug therapy is clearly not a contraindication to acute or chronic exercise as long as the potential benefits and complications of exercise and drug interaction are considered.

Angina Pectoris↗
PubMed1987

Drug therapy in the elderly: special considerations.

The tendency toward polypharmacy in the elderly, combined with age-related physiologic changes, increases the risk for adverse effects resulting from the interference of one drug regimen with another. Altering drug dosages for concomitant drug regimens is important if the patient is to gain maximum benefit from the drugs with minimal adverse effects. Altered pharmacokinetics in the elderly, impaired drug response, and adverse effects of polypharmacy are each discussed with respect to drug absorption, distribution, metabolism, and elimination.

Aged↗
PubMed1986

Efficacy of clonidine as transdermal therapeutic system: the international clinical trial experience.

Worldwide clinical trial data concerning the pharmacokinetic and pharmacodynamic characteristics of the clonidine transdermal therapeutic system (TTS) are reviewed with reference to its antihypertensive efficacy. The amount of clonidine delivered to the systemic circulation is a direct function of TTS size. After initial patch application, there is a delay of 2 to 3 days before the onset of action, but after removal of the patch, plasma clonidine levels decline slowly, at an elimination half-life of about 20 hours. Evaluation in approximately 2000 patients with mild to moderate hypertension has shown that the bioavailability of transdermal clonidine is comparable to that of oral clonidine and that equivalent blood pressure reductions are achieved. The rate at which dose increases were found necessary to maintain adequate blood pressure control over extended periods reflects a low incidence of tolerance to this new once-a-week dosage form of clonidine, and there has been little evidence of rebound hypertension after discontinuation of TTS treatment.

Administration, Cutaneous↗
PubMed1986

Plasma norepinephrine in exercise-induced ventricular tachycardia.

The relation between plasma norepinephrine levels and the occurrence of ventricular tachycardia during exercise testing was prospectively evaluated in 17 patients. Ten patients had reproducible ventricular tachycardia exclusively during exercise or recovery, or both; 7 patients had ventricular tachycardia only during ambulatory electrocardiographic monitoring. The two groups did not differ in age, exercise duration, left ventricular ejection fraction at rest, heart rate throughout the exercise protocol, rest QTc interval, change in QTc interval during exercise, the presence of coronary artery disease or exercise-related myocardial ischemia. Furthermore, there was no difference between groups in plasma norepinephrine levels at rest, peak exercise or in the recovery period. Myocardial ischemia was detectable by thallium perfusion scan in only 2 of the 10 patients with exercise-induced ventricular tachycardia. The 10 patients with exercise-induced ventricular tachycardia underwent repeat exercise testing immediately after maximal intravenous beta-adrenergic blockade with propranolol. Although they had no change in exercise duration, ventricular tachycardia did not occur in 9 of these 10 patients. Plasma norepinephrine levels were significantly decreased compared with levels before beta-adrenergic blockade (p less than 0.0002). Thus, plasma norepinephrine levels do not distinguish patients with reproducible exercise-induced ventricular tachycardia from otherwise comparable patients. Propranolol is highly effective in abolishing this arrhythmia and this effect is associated with decreased norepinephrine levels.

Adult↗
PubMed1986

Critical therapeutic categories: a contraindication to generic substitution?

All 50 states either permit or require a pharmacist to substitute a generic drug for a prescribed brand-name drug unless the physician specifically notes on the prescription form that substitution is not to be made. In certain critical therapeutic categories and for certain patient populations, each substitution poses the risks of treatment failure and of increased toxicity. The therapeutic categories include cardiovascular drugs, psychotropic agents, and anticonvulsants. Additional potential therapeutic categories include cardiovascular drugs, psychotropic agents, and anticonvulsants. Additional potential therapeutic categories include low-dose oral contraceptives, bronchodilating agents, oral diuretics, and oral anticoagulants. The populations at risk include debilitated or elderly patients with abnormal gastrointestinal, renal, or hepatic function. The FDA's approach to approval of generic drugs, based primarily on the demonstration of bioequivalence, is considered by many professionals as likely to result in excessive variability among treated patients. Depending on the particular rule defining bioequivalence, indiscriminate switching among generic versions of a brand-name drug potentially could result in 40% to 60% differences in rate or extent of absorption. For drugs that require careful titration to assure efficacy and lack of toxicity, such variability can have important consequences. The FDA is now reviewing its policies for approval of generic drugs. Until the matter is resolved, however, caution should be exercised when prescribing or dispensing drugs that can be substituted. Indiscriminate switching among generic products should be avoided, especially for drugs in the critical therapeutic categories and for drugs prescribed for elderly or debilitated patients.

Aged↗
PubMed1985

Clinical pharmacology, pharmacodynamics and interactions with esmolol.

The clinical pharmacology and pharmacodynamic data from several clinical trials are summarized. The pharmacokinetic profile of esmolol alone and in the presence of digoxin, morphine and warfarin was studied. Conversely the effect of esmolol on these drugs was monitored. No clinically important effects were observed on vital signs, blood chemistry or hematology. The pharmacokinetic interactions associated with administration of these drug combinations were statistically significant in several cases, but they were not considered to be of clinical importance.

Adrenergic beta-Antagonists↗
PubMed1985

Conversion from intravenous to oral mexiletine in the acute management of repetitive ventricular arrhythmia.

We evaluated the safety and efficacy of intravenous mexiletine and a method for converting from intravenous to oral mexiletine therapy. Fifteen patients with repetitive ventricular ectopy (13 had ventricular tachycardia) received intravenous mexiletine at a rate of 10 mg/min for 30 to 60 minutes. Ventricular ectopy was suppressed with minimal side effects in 10 of 15 subjects. Oral mexiletine was begun immediately after completion of the intravenous infusion at a dose of 10 mg/kg/24 hr in the 10 responders to intravenous therapy. In eight, the oral dose was effective in suppressing the arrhythmia, but it induced side effects in three of them. In one of these three, dose reduction resulted in adequate arrhythmia control with acceptable toxicity. In the two who did not respond to the original dose, a larger dose (15 mg/kg/24 hr) induced arrhythmia control with acceptable side effects in one subject. Thus rapid control of nonsustained repetitive ventricular arrhythmia can be achieved with intravenous mexiletine in about two thirds of patients, and conversion to oral therapy can often be achieved smoothly without significant arrhythmia recurrence.

Administration, Oral↗
PubMed1985

The effect of renal function on enalapril kinetics.

Enalapril maleate (MK-421), a nonmercapto-containing angiotensin converting enzyme (ACE) inhibitor, is converted in vivo to enalaprilat (MK-422), the active diacid. We evaluated serum profiles and urinary excretion of oral enalapril maleate in patients with renal disease (group I, creatinine clearance less than 3 ml/min, patients undergoing dialysis, n = 10; group II, creatinine clearance 10 to 79 ml/min, n = 9) compared with healthy subjects (group III, creatinine clearance greater than 80 ml/min, n = 10). Group I received a 10 mg dose during a day while not receiving dialysis and a 10 mg dose 1 hour before dialysis 2 weeks later. Groups II and III received a single 10 mg dose. Blood samples and urine were collected for 48 hours. Impaired renal function resulted in elevated serum and plasma concentrations of enalapril maleate and decreased excretion rates and urinary recovery of enalapril maleate and enalaprilat. The data suggest an apparent increase in the extent of metabolism of enalapril maleate to enalaprilat or an increase in nonrenal elimination of unchanged enalapril maleate in renal disease compared with normal health. Enalaprilat was dialyzable.

Administration, Oral↗
PubMed1985

Hypertension update for the 1980s.

The treatment of hypertension must be based on pathophysiologic grounds. The drugs that have been used in the classic stepped-care approach are still useful, but the rationale for their usage should not be based on the presumption that all hypertension is mediated by salt and water. Thus, the adolescent obtains greater benefits from a beta-adrenergic blocking drug or a centrally acting antihypertensive. The individual with heart failure may benefit more from a converting enzyme inhibitor than a vasodilator. In cerebrovascular disease with hypertension, dosage must be reduced owing to the enhanced sensitivity of response. New drugs are discussed, and their place in the armamentarium is evaluated.

Adolescent↗
PubMed1985

Transdermal clonidine in the treatment of adolescent hypertension.

The effectiveness of transdermally administered clonidine in normalizing blood pressure in 22 adolescents with sustained diastolic hypertension was studied. The clonidine transdermal device consisted of an adhesive disc which delivered a low, but continuous, dose of drug through the skin for at least 1 week. Following a placebo disc, subjects received clonidine with increasing titration every 2 weeks until blood pressure reduction goals (90th percentile) were achieved. In 21 of 22 subjects blood pressure goals were achieved and maintained for 8 weeks of stable dose. Side effects were minimal.

Administration, Topical↗
PubMed1984

Mechanisms of action and the clinical pharmacology of beta-adrenergic blocking drugs.

At present more than 20 beta-adrenergic blocking drugs are commercially available in Western Europe, and six are available in the United States. The clinical indications for their usage include hypertension, arrhythmias, ischemic heart disease, thyrotoxicosis, migraine headaches, glaucoma, and anxiety states. We will review the mechanisms suggested for the antihypertensive action of beta-adrenergic blocking drugs as well as these agents' clinical pharmacologic aspects. In general, the pharmacodynamic effects of the beta blocking drugs are quite similar, yet the properties of biotransformation, including pharmacokinetics, tend to be distinguishing features.

Adrenergic beta-Antagonists↗
PubMed1984

Effects of nifedipine and verapamil on isometric and dynamic exercise in normal subjects.

Effects of single- and multiple-dose nifedipine and verapamil in 10 healthy men were compared with the effect of placebo during static and dynamic physical activity. Blood pressure (BP), heart rate (HR), and plasma catecholamine and plasma potassium levels were assessed and quantified at rest and at peak levels of 50% handgrip and at rest and peak treadmill activity during placebo, single- and at 2 multiple-dose levels of each of the drugs. Peak BP responses were blunted by a maximal dosage of 120 mg of verapamil administered twice daily during static activity. No blunting of HR response was observed. BP and HR did not change significantly at any dosage level of nifedipine during static exercise. During isotonic exercise the only significant alteration was a progressive decrease in the peak exercise HR with both verapamil and nifedipine. The plasma potassium level increased with both static and dynamic activity but to no greater level than that seen with placebo. Plasma norepinephrine concentration increased at rest after administration of maximal dosage of nifedipine during both isometric and isotonic phases of the study. This is probably related to the underlying mild to moderate increase in sympathetic tone induced by nifedipine. Overall, the hemodynamic responses to exercise are not blunted with calcium-channel antagonists at the dosages studied.

Blood Pressure↗
PubMed1984

Influence of uremia and hemodialysis on the plasma protein binding of tolmetin.

Binding of the nonsteroidal anti-inflammatory drug, tolmetin, to plasma from uremic patients before hemodialysis and from healthy subjects was compared using microequilibrium dialysis techniques. The percent age of free tolmetin was 2-15 times greater in plasma from uremic patients (1.33-3.08%) than in plasma from healthy volunteers (0.37-0.63%) at all three concentrations of the drug studied (0.5, 5 and 50 micrograms/ml). The reduced plasma binding of tolmetin in plasma from uremic patients was associated with significantly higher dissociation constants for the high-affinity tolmetin binding site on plasma albumin. When added at concentrations of 2.0 mM oleic, stearic and palmitic acids, 3 representative nonesterified fatty acids (NEFA) were found to significantly enhance tolmetin binding to plasma proteins. No differences in total plasma NEFA concentrations were observed between uremic patients before hemodialysis and healthy subjects. However, higher total NEFA concentrations in plasma from uremic patients after hemodialysis were accompanied by increased tolmetin binding. Possible NEFA effects on tolmetin binding could not be dissociated from other influences, such as the removal of endogenous binding inhibitors during hemodialysis.

Adult↗
PubMed1984

The clinical pharmacology of antihypertensive drugs.

Antihypertensive drugs act centrally (methyldopa, clonidine, guanabenz), peripherally (prazosin, guanadrel, guanethedine, hydralazine, minoxidil), centrally and peripherally (beta-adrenergic blocking drugs) and systemically [angiotensin converting enzyme (ACE) inhibitors and diuretics]. Centrally-acting antihypertensives decrease blood pressure by diminishing sympathetic outflow from the vasomotor centre. Peripherally-acting antihypertensives act by depleting or inhibiting the release of catecholamines from the peripheral nerve ending or altering the response at alpha 1- and alpha 2-receptor sites. Beta-adrenergic blocking drugs act through a variety of mechanisms by either decreasing cardiac output, decreasing renin release, inhibiting prejunctional release of norepinephrine or through central mechanisms. Diuretics act as indirect vasodilators by depleting salt and water not only within the intravascular compartment but within the intramural portion of the arteriole, thereby diminishing its responsiveness to catecholamine and angiotensin II stimulation. ACE inhibitors such as captopril and enalapril act by inhibiting the conversion of angiotensin I to angiotensin II thereby decreasing the vasoconstrictor effect of angiotensin II and the aldosterone production secondary to angiotensin II stimulation. The main differences between captopril and enalapril is that enalapril does not possess the potentially toxic sulphydryl group and can be given twice-daily. Both drugs may show accumulation in patients with impaired renal function.

Adrenergic alpha-Agonists↗